LncRNA DIO3OS regulated by TGF-β1 and resveratrol enhances epithelial mesenchymal transition of benign prostatic hyperplasia epithelial cells and proliferation of prostate stromal cells

  • Transl Androl Urol. 2021 Feb;10(2):643-653. doi: 10.21037/tau-20-1169.
Yanbo Chen  1 ,  Hui Xu  2 ,  Chong Liu  1 ,  Meng Gu  1 ,  Ming Zhan  1 ,  Qi Chen  1 ,  Zhong Wang  1
Affiliations
  • 1. Department of Urology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2. Department of Emergency, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
PMID: 33718067 DOI: 10.21037/tau-20-1169
Abstract

Background: The etiopathogenesis of benign prostatic hyperplasia (BPH) is extremely complicated which involving epithelial-mesenchymal transition (EMT) of epithelial cells and growth of stromal cells. Long non-coding RNAs (lncRNAs) belong to a group of noncoding RNAs which has been widely studied in Other Diseases but rarely in BPH. Here, we intend to investigate the roles of a lncRNA DIO3 opposite strand (DIO3OS) in BPH progression.

Methods: BPH-1 cells were used to study EMT and WPMY-1 cells were applied to study proliferation induced by TGF-β1, resveratrol, DIO3OS and miRNAs.

Results: DIO3OS was over-expressed in BPH tissues and could be upregulated by Transforming growth factor beta 1 (TGF-β1) and downregulated by resveratrol. SMAD2/SMAD3/SMAD4 complex could bind to the DIO3OS promotor region and thereby enhanced its transcription which was responsible for the regulation of TGF-β1 and resveratrol on DIO3OS expression. TGF-β1 promoted BPH-1 cells EMT and WPMY-1 cells proliferation via DIO3OS and this effect could be blocked by resveratrol. MiR-656-3p and miR-485-5p were targets of DIO3OS and DIO3OS promoted BPH-1 cells EMT and WPMY-1 cells proliferation via miR-656-3p and miR-485-5p. Connective tissue growth factor (CTGF) and zinc finger e-box binding homeobox 1 (ZEB1) were confirmed to be targets of both miR-656-3p and miR-485-5p and could be modulated by TGF-β1, resveratrol, DIO3OS, miR-656-3p and miR-485-5p.

Conclusions: DIO3OS is highly expressed in BPH tissues and regulated by TGF-β1 as well as resveratrol in a Smads dependent manner. DIO3OS facilitates BPH-1 cells EMT and WPMY-1 cells proliferation by upregulating CTGF and ZEB1 via miR-656-3p and miR-485-5p.

Keywords
Benign prostatic hyperplasia (BPH); DIO3 opposite strand (DIO3OS); epithelial-mesenchymal transition (EMT); long non-coding RNA (lncRNAs); miRNAs.
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